Tuberculosis remains a serious and common disease worldwide. Worldwide emergence of multi-antibiotic resistant strains, accelerated by the passage of M. tuberculosis in patients with AIDS, poses a public health problem. Although it is the most frequently used vaccine in the world, there is no scientifically-based evidence that BCG prevents primary pulmonary tuberculosis (the most common disease caused by M. tuberculosis). The protective effect of BCG vaccination against meningitis in children has not been related to an antigen/s or a host immune component. Research into a new vaccine is based upon the similarity of primary infection caused by M. tuberculosis with that of capsulated bacterial respiratory pathogens, viz: 1) tuberculous meningitis has a similar age distribution as meningitis caused by meningococci, pneumococci and Haemophilus influenzae type b; 2) M. tuberculosis and other mycobacteria have a polysaccharide capsule in vitro and in vivo; and 3) Protein components prolonged survival of but do not protect animals against challenge with wild-type M. tuberculosis. We purified a glucan and an arabinomannan from a saline extract of M. tuberculosis. The polysaccharides were conjugated to P. aeruginosa recombinant protein A and shown to be immunogenic in mice and in rabbits. Antibodies induced by these conjugates, whether actively induced or passively administered did not protect mice against pulmonary challenge with M. tuberculosis. Antibodies to both polysaccharides in adults, measured by ELISA, showed that patients with tuberculosis had much higher levels than normals. A standardized and quantitative assay for diagnosis of tuberculosis with these polysaccharide antigens is underway. Both the glucan and arabinomannan conjugates are being evaluated for their protective activity in mice in collaboration with CBER, FDA.